Download An Open Study of Botulinum-A Toxin Treatment of Idiopathic

An Open Study of Botulinum-A Toxin Treatment of Idiopathic Trigeminal
Neuralgia
Karim Nikkhah1 (MD); Mohammad Taghi Farzadfard1 (MD); Payam Sasannejad1* (MD); Ali Ghabeli Juibary2 (MD);
Marzieh Taheri3 (MD); Samira Aminzadeh2 (MD)
1.
Department of Neurology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Neurology, Student Research Committee, School of Medicine, Mashhad University of Medical Sciences,
Mashhad, Iran.
3.
Neurologist, Khorasan, Iran.
2.
ARTICLEINFO
ABSTRACT
Article type:
Introduction: Trigeminal Neuralgia (TN) is a unilateral, recurrent, sharp
Original Article
facial pain disorder that is limited to the distribution of divisions of the
trigeminal nerve. The aim of this study was to evaluate the efficacy of
Botulinum neurotoxin type A (BTX-A) for alleviating the frequency and
severity of TN pain.
Materials and Methods: This trial was performed as a before and after
study. We treated 31 patients (15 male and 16 female) with mean age of 52
year old that their diagnosis was made at least 4.5 years before. We injected
BTX-A in various parts of face and particularly in the origin of mandibular and
maxillary branches of trigeminal nerve. Injection volume was determined by
the necessity and pain intensity measured with visual analog scale up to 100U.
Patients were evaluated before and after the injection and were followed after
week, and each month, for a three months period. Other related variables were
recorded such as: toxin complications, pain status variations by brushing,
chewing, cold weather and patient’s satisfaction with their therapy.
Results: showed that after injection, pain intensity and frequency decreased
after tooth brushing, chewing and cold weather (P<0.0001). Median of pain
intensity decreased from 10 to 2 in all cases. Only 6% of patients affected to
transient asymmetry and other complications were not observed. After 3
months of injection 71% of patients were inclined to reinjection.
Conclusion: BTX-A could be used as an effective and safe treatment method
for drug resistant TN. Also it can be used in patients who are not satisfied with
oral anticonvulsants.
Article history:
Received: 22-Oct-2014
Accepted: 11-Nov-2014
Keywords:
Trigeminal neuralgia
Botulinum neurotoxin type A
Facial pain
Please cite this paper as:
Nikkhah N, Farzadfard MT, Sasannejad P, Ghabeli Juibary A, Taheri M, Aminzadeh S. An Open Study of Botulinum-A Toxin
Treatment of Idiopathic Trigeminal Neuralgia. Patient Saf Qual Improv. 2015; 3(3):243-246.
Introduction
Trigeminal Neuralgia (TN), as described by the
International Association for the Study of Pain (IASP),
is a unilateral facial pain disorder that is described by
brief, sharp, paroxysmal lancinating pains that are
recurrent, and limited to the distribution of divisions of
the trigeminal nerve (1). The prevalence of this
disorder is approximately 1 in 25000, and it is a little
more common in women than in men. It also affects
middle-aged or older people more frequently (2).
In the latest classification of the International
Headache Society, a distinction was made between
classical and symptomatic TN: Classical TN (CTN)
includes idiopathic cases in addition to those with
vascular compression of the fifth cranial nerve;
Symptomatic TN (STN) is detected in cases secondary
to multiple sclerosis, tumors, and structural
abnormalities of the skull base (3). The pain attacks can
be either spontaneous, or precipitated by specific
coetaneous stimuli within specific “trigger zones,”
leaving some patients unable to eat, drink, brush their
teeth, or shave their faces (4).
Diverse interventions have been tried to decrease the
pain and reduce the frequency of pain attacks in TN.
Anticonvulsive pharmacotherapy remains the firstline treatment. Carbamazepine is often used for pain
control (5).
© 2014 mums.ac.ir All rights reserved.
*Corresponding Author: Payam Sasannejad, Department of Neurology, Faculty of Medicine, Mashhad University of Medical
Sciences, Mashhad, Iran. Email: [email protected]
Nikkhah et al
Botulinum neurotoxin type A (BTX-A) has been
successfully utilized to treat pains such as migraine and
occipital neuralgia. BTX-A has recently gained
popularity in treating patients with TN, more
specifically TN refractory to medical and surgical
interferences (6-12).
These patients had been previously labeled surgical
candidates; however, BTX-A treatment offer a less
invasive option for pain alleviation with good results
and minimal side effects.
The history should definitively rule out other causes
of facial pain. Because of the association with multiple
sclerosis, patients should be asked about neurologic
symptoms (e.g., dizziness, focal weakness, ataxia,
vision changes) and other atypical symptoms that might
lead to another diagnosis.
The recognition and treatment of trigger zones on the
face will provide the most benefit to the patient. Wide
variations have been published in the literature, with
one case report documenting the administration of 100
U to a single trigger site (3).
Frequency of administration also needs to be
individualized. Duration of effect in the literature
ranges from weeks to six months. Initial treatments
should be accompanied by a pain diary, which enables
the patient and physician to track the waning and
waxing of symptoms with treatment.
Side effects of BTX-A injections are generally a
result of its effect on motor synapses, including the
possibility of facial weakness and asymmetry after
treatment. Facial edema, erythema, and hypesthesia
been reported (4).We designed an open label trial to
study the efficacy of BTX-A for decreasing the TN
pain.
Materials and Methods
During 24 months 34 patients who met the inclusion
criteria (idiopathic TN on oral pharmacotherapy and
refractory painful attacks), were included in the trial
among them three patients excluded because of
multiple sclerosis (two patients) and vascular loop (one
patient) etiology in study period so 31 patients
completed the study.
The neurologist performed a careful head and neck
examination, with emphasis on the neurologic feature.
An otologic, oral, and Temporomandibular Joint
(TMJ) examination was done to look for other causes
of facial pain. Facial nerve function and facial
symmetry documented prior to the injections in the
neurologic head and neck examination.
Magnetic Resonance Imaging (MRI) of the brain
performed for all patients presenting with trigeminal
neuralgia.
The history definitively ruled out other causes of
facial pain and oral therapies was continued before and
after injection. The patients were refractory to
conventional medical therapy and they had attacks
despite oral pharmacotherapy.
Subjects with a known hypersensitivity to the toxin,
244
Botulinum-A Toxin in Trigeminal Neuralgia
and diseases that might interfere with neuromuscular
transmission, such as myasthenia gravis, EatonLambert syndrome, amyotrophic lateral sclerosis,
patients taking aminoglycosides, and patients with
facial skin infection or pregnant or lactating women
excluded from trial.
After their inclusion in this open label study by
signing in an informed consent form, botulinum toxin
type A (Dysport®) was injected intradermal in the
painful region, particularly in the trigger zones.
Each vial was diluted with 2 ml of standard sterile
saline solution and injected in trigger zone.
A 28 gauge insulin needle was used for
administration toxin in all patients and one expert
neurologist performed the injections in all patients.
Initial dose was 100 units of botulinum toxin type A
(Dysport®) in all of our patients. Each vial contained
500 units. We draw a grid on the patient’s face in the
region of allodynia or hyperesthesia. Next, 2.5 unit
(U)/0.1 cc intradermal injections of BTX-A per
centimeter length were administered within the grid.
The injection continued along with a line of sharp
lancinating pain pathway on the face. If the trigger
point was on the inner mucosa of mouth or gum,
nearest point on the facial skin selected for injection.
Toxin was injected in the first visit. In patients with
mandibular root involvement, a larger amount of the
toxin was injected in the masseter in order to stay away
from undesired cosmetic side effects.
The population was evaluated one week, one, two
and three months after the injections in the clinic and
pain intensity and adverse effects were asked.
Severity of pain associated with tooth brushing,
chewing and cold weather was recorded based on
visual analogue scale.
Friedman test was performed using the Statistical
Package for the Social Sciences software (SPSS
version 21, Chicago, IL).Protocol approved by the
regional ethics committee of Mashhad university of
Medical Sciences.
Results
Thirty one patients (15 men, 16 women) with an age
average of 52 years old participated in this study with
an average amount of about 4.5 years time period
which had been passed since the diagnosis of
trigeminal neuralgia(between one and twenty years).
Twenty nine patients (94%) were using
Carbamazepine, fourteen patients were using
Gabapentin and four patients were using Baclofen.
Sixteen patients (52%) were on combination therapy.
Pharmacotherapy continued after botulinum toxin
type A (Dysport®) injection.
In 30 patients pain was aggravated after tooth
brushing and chewing, in 27 patients pain was
aggravated after cold weather exposure, median of pain
severity in all categories before intervention was 10 and
after BTX-A injection, median of pain severity reached
two. (Table1-3).
Patient Saf Qual Improv, Vol. 3, No. 3, Sum 2015
Nikkhah et al
Botulinum-A Toxin in Trigeminal Neuralgia
Table1: Median pain intensity before and after one week, one,
two and three month of Botulinum-A toxin injection
Pain
Pain
Pain
Pain
Pain
intensity
intensity intensity intensity intensity
after
before
after one after one after two
three
intervention week
month months
months
Total
number
Median
Minimum
Maximum
31
31
31
31
31
10
8
10
2
0
10
2
0
10
2
0
10
2
0
10
Table2: Median pain intensity with brushing before and after one
week, one, two and three month of Botulinum-A toxin injection
Pain
Pain
Pain
Pain
Pain
intensity
intensity
intensity
intensity intensity
with
with
with
with
with
brushing
brushing
brushing
brushing brushing
after one
after
before
after one after two
week
three
intervention
month months
months
Total
number
Median
Minimum
Maximum
31
31
31
31
31
10
0
10
2
0
10
2
0
10
2
0
10
2
0
10
Table3: Median pain intensity with chewing before and after one
week, one, two and three month of Botulinum-A toxin injection
Pain
Pain
Pain
Pain
Pain
intensity
intensity
Intensity
intensity intensity
with
with
with
with
with
chewing
chewing
chewing
chewing chewing
after one
after
before
after one after two
week
three
intervention
month months
months
Total
number
Median
Minimum
Maximum
31
31
31
31
31
10
0
10
2
0
10
2
0
10
2
0
10
2
0
10
Median of Pain Severity
Severity of pain decreased significantly after BTX-A
injection after tooth brushing, chewing and cold
weather exposure (P<0.0001) (Figure).
12
10
8
6
4
2
0
Before weeks 1 month 1 month 2 month 3
injection after
after
after
after
injection injection injection injection
Time
Figure: Median of pain intensity by chewing, tooth
brushing and exposure to cold weather.
Of total of 31 patients 22(71%) patients were inclined
to reinjection after 3 months of follow up. Only two
patients (6%) affected to transient facial asymmetry
(one month duration) and other complications were not
observed in our patients.
Discussion
Our findings demonstrate the beneficial effects of
BTX-A in pain control in cases of idiopathic TN, which
supports previous findings as well as those by Piovesan
et al. and Borodic and Acquadro (6, 13).
However, many aspects remain unclear including the
extremely rapid action of pain management by the
toxin, within minutes of the inoculation, in some of our
cases.
Alternatively, in most of our patients pain reappeared
after 60 days in contrast to the motor benefit usually
lasting between three and six months depending both
on an individual basis and the underlying cause of
muscle hyperactivity.
However, in other patients’ pain improvement lasted
up to three months.
BTX-A has repeatedly shown its efficacy for the
treatment of headache in several clinical trials, but
there still is ambiguity as to how botulinum toxin type
A should be best used for treating headache, and which
patients are best appropriate for this treatment (14, 15).
In addition, myofacial pain syndrome, neuropathic
pain disorders, fibromyalgia, and "off" painful dystonia
in Parkinson's disease, among others, have also been
reported to respond to BTX-A injections (16-20).
Conclusion
Our study suggests that BTX-A characterizes a safe
and effective treatment modality.
BTX-A could be a useful therapeutic method in the
management of both TN and probably other similar
conditions. BTX-A provides a very fast and long-term
benefit, and is otherwise devoid of systemic
consequences.
Additional double-blind studies including an
appropriate number of patients are required to validate
our findings and to explore whether higher doses
provide a more sustained effect and optimize injection
sites. Further studies will help to clarify ideal injection
schedules and approaches.
Acknowledgment
We thank all patients who participated in this study.
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